RT Journal
A1 Nicholls SJ, Brewer H, Kastelein JP, et al
T1 Effects of the cetp inhibitor evacetrapib administered as monotherapy or in combination with statins on hdl and ldl cholesterol: A randomized controlled trial
JF JAMA
JO JAMA
YR 2011
FD November 16
VO 306
IS 19
SP 2099
OP 2109
DO 10.1001/jama.2011.1649
UL http://dx.doi.org/10.1001/jama.2011.1649
AB Context 
                  Interest remains high in cholesteryl ester transfer protein (CETP) inhibitors as cardioprotective agents. Few studies have documented the efficacy and safety of CETP inhibitors in combination with commonly used statins.Objective 
                  To examine the biochemical effects, safety, and tolerability of evacetrapib, as monotherapy and in combination with statins, in patients with dyslipidemia.Design, Setting, and Participants 
                  Randomized controlled trial conducted among 398 patients with elevated low-density lipoprotein cholesterol (LDL-C) or low high-density lipoprotein cholesterol (HDL-C) levels from April 2010 to January 2011 at community and academic centers in the United States and Europe.Interventions 
                  Following dietary lead-in, patients were randomly assigned to receive placebo (n = 38); evacetrapib monotherapy, 30 mg/d (n = 40), 100 mg/d (n = 39), or 500 mg/d (n = 42); or statin therapy (n = 239) (simvastatin, 40 mg/d; atorvastatin, 20 mg/d; or rosuvastatin, 10 mg/d) with or without evacetrapib, 100 mg/d, for 12 weeks.Main Outcome Measures 
                  The co–primary end points were percentage changes from baseline in HDL-C and LDL-C after 12 weeks of treatment.Results 
                  The mean baseline HDL-C level was 55.1 (SD, 15.3) mg/dL and the mean baseline LDL-C level was 144.3 (SD, 26.6) mg/dL. As monotherapy, evacetrapib produced dose-dependent increases in HDL-C of 30.0 to 66.0 mg/dL (53.6% to 128.8%) compared with a decrease with placebo of −0.7 mg/dL (−3.0%; P < .001 for all compared with placebo) and decreases in LDL-C of −20.5 to −51.4 mg/dL (−13.6% to −35.9%) compared with an increase with placebo of 7.2 mg/dL (3.9%; P < .001 for all compared with placebo). In combination with statin therapy, evacetrapib, 100 mg/d, produced increases in HDL-C of 42.1 to 50.5 mg/dL (78.5% to 88.5%; P < .001 for all compared with statin monotherapy) and decreases in LDL-C of −67.1 to −75.8 mg/dL (−11.2% to −13.9%; P < .001 for all compared with statin monotherapy). Compared with evacetrapib monotherapy, the combination of statins and evacetrapib resulted in greater reductions in LDL-C (P <.001) but no greater increase in HDL-C (P =.39). Although the study was underpowered, no adverse effects were observed.Conclusions 
                  Compared with placebo or statin monotherapy, evacetrapib as monotherapy or in combination with statins increased HDL-C levels and decreased LDL-C levels. The effects on cardiovascular outcomes require further investigation.Trial Registration 
                  clinicaltrials.gov Identifier: NCT01105975